Deep Learning-Enabled Multiplexed Point-of-Care Sensor using a Paper-Based Fluorescence Vertical Flow Assay.

Multiplexed computational sensing with a point-of-care serodiagnosis assay to simultaneously quantify three biomarkers of acute cardiac injury is demonstrated. This point-of-care sensor includes a paper-based fluorescence vertical flow assay (fxVFA) processed by a low-cost mobile reader, which quantifies the target biomarkers through trained neural networks, all within <15 min of test time using 50 µL of serum sample per patient. This fxVFA platform is validated using human serum samples to quantify three cardiac biomarkers, i.e., myoglobin, creatine kinase-MB, and heart-type fatty acid binding protein, achieving less than 0.52 ng mL-1 limit-of-detection for all three biomarkers with minimal cross-reactivity. Biomarker concentration quantification using the fxVFA that is coupled to neural network-based inference is blindly tested using 46 individually activated cartridges, which shows a high correlation with the ground truth concentrations for all three biomarkers achieving >0.9 linearity and <15% coefficient of variation. The competitive performance of this multiplexed computational fxVFA along with its inexpensive paper-based design and handheld footprint makes it a promising point-of-care sensor platform that can expand access to diagnostics in resource-limited settings.

Identification of alkaloids from Justicia adhatoda as potent SARS CoV-2 main protease inhibitors: An in silico perspective.

The COVID-19 pandemic, caused by SARS CoV-2, is responsible for millions of death worldwide. No approved/proper therapeutics is currently available which can effectively combat this outbreak. Several attempts have been undertaken in the search of effective drugs to control the spread of SARS CoV-2 infection. The main protease (Mpro), key component for the cleavage of the viral polyprotein, is considered to be one of the important drug targets for treating COVID-19. Various phytochemicals, including polyphenols and alkaloids, have been proposed as potent inhibitors of Mpro. The alkaloids from leaf extracts of Justicia adhatoda have also been reported to possess anti-viral activity. But whether these alkaloids exhibit any inhibitory effect on SARS CoV-2 Mpro is far from clear. To explore this in detail, we have adopted computational approaches. Justicia adhatoda alkaloids possessing proper drug-likeness properties and two anti-HIV drugs (lopinavir and darunavir; having binding affinity -7.3 to -7.4 kcal/mol) were docked against SARS CoV-2 Mpro to study their binding properties. Only one alkaloid (anisotine) had interaction with both the catalytic residues (His41 and Cys145) of Mpro and exhibited good binding affinity (-7.9 kcal/mol). Molecular dynamic simulations (100 ns) revealed that Mpro-anisotine complex is more stable, conformationally less fluctuated; slightly less compact and marginally expanded than Mpro-darunavir/lopinavir complex. Even the number of intermolecular H-bonds and MM-GBSA analysis suggested that anisotine is a more potent Mpro inhibitor than the two previously recommended antiviral drugs (lopinavir and darunavir) and may evolve as a promising anti-COVID-19 drug if proven in animal experiments and on patients.

DNA minor groove binding of a well known anti-mycobacterial drug dapsone: A spectroscopic, viscometric and molecular docking study.

Dapsone is a sulfone drug mainly used as anti-microbial and anti-inflammatory agent for the treatment of various diseases including leprosy. Recently, its interaction with protein (bovine serum albumin) is evidenced. But, the binding propensity of this anti-mycobacterial drug towards DNA is still unknown. Also, the mode of dapsone-DNA interaction (if any) is still an unknown quantity. In this study, we have taken a thorough attempt to understand these two unknown aspects using various biophysical and in silico molecular docking techniques. Both UV-visible and fluorescence titrimetric studies indicated that dapsone binds to CT-DNA with a binding constant in order of 104 M-1. Circular dichroism, thermal denaturation and viscosity experiments revealed that dapsone binds to the grooves of CT-DNA. Competitive DNA binding studies clearly indicated the minor groove binding property of this anti-mycobacterial drug. Molecular docking provided detailed information about the formation of hydrogen bonding in the dapsone-DNA complex. This in silico study further revealed that dapsone binds to the AT-rich region of the minor groove of DNA having a relative binding energy of -6.22 kcal mol-1. Overall, all these findings evolved from this study can be used for better understanding the medicinal importance of dapsone.

Adsorption of Fluoroquinolone Antibiotics at the Gas-Liquid Interface Using Ionic Surfactants.

The overuse of antibiotics in today's society has resulted in high concentrations of pharmaceutical contaminants in the natural environment. In this work, we investigated the surfactant-mediated adsorption of fluoroquinolone (FQ) antibiotics at the gas-liquid interface and their separation using a semi-batch foam fractionation process. FQs being a zwitterionic compound have an affinity to bind with both cationic and anionic surfactants. The adsorption of FQs to the gas-liquid interface was investigated using a cationic cetyltrimethylammonium bromide (CTAB) and anionic sodium dodecyl sulfate (SDS) surfactant. Ciprofloxacin (CF) was chosen as a model FQ antibiotic. The adsorption properties of the surfactant systems and CF were characterized using pendant-drop tensiometry and surface excess analysis. It was found that CF partitions to the gas-liquid interface more readily in the presence of SDS compared to CTAB. This was also corroborated in the foam fractionation experiments. At optimum operating conditions, CF showed a higher removal efficiency with SDS (96.3%) compared to CTAB (52%). In spite of strong molecular interactions between CTAB and CF, the preferential adsorption of DS--CF complexes was far greater than CTA+-CF complexes. At optimized operating conditions, using SDS as the surfactant, other FQs such as norfloxacin, levofloxacin, and ofloxacin were recovered up to 97.9, 91.7, and 96.7%, respectively, with effluent concentration less than 100 nM. Overall, the work demonstrates foam fractionation as a novel and environment-friendly gas-liquid separation technique for the targeted removal of FQ antibiotics from waterbodies.

Monte Carlo Type Simulations of Mineralized Collagen Fibril Based on Two Scale Asymptotic Homogenization.

A multiscale model for mineralized collagen fibril (MCF) is proposed by taking into account the uncertainties associated with the geometrical properties of the mineral phase and its distribution in the organic matrix. The asymptotic homogenization approach along with periodic boundary conditions has been used to derive the effective elastic moduli of bone's nanostructure at two hierarchical length scales, namely: microfibril (MF) and MCF. The uncertainties associated with the mineral plates have been directly included in the finite element mesh by randomly varying their sizes and structural arrangements. A total of 100 realizations for the MCF model with random distribution have been generated using an in-house MATLAB code, and Monte Carlo type of simulations have been performed under tension load to obtain the statistical equivalent modulus. The deformation response has been studied in both small (≤10%) and large (≥10%) strain regimes. The stress transformation mechanism has also been explored in MF which showed stress relaxation in the organic phase upon different stages of mineralization. The elastic moduli for MF under small and large strains have been obtained as 1.88 and 6.102 GPa, respectively, and have been used as an input for the upper scale homogenization procedure. Finally, the characteristic longitudinal moduli of the MCF in the small and large strain regimes are obtained as 4.08 ± 0.062 and 12.93 ± 0.148 GPa, respectively. All the results are in good agreement to those obtained from previous experiments and molecular dynamics (MD) simulations in the literature with a significant reduction in the computational cost.

Fracture Mechanism and Fracture Toughness at the Interface Between Cortical and Cancellous Bone.

The microstructure at the interface of cortical and cancellous bone is quite complicated. The fracture mechanisms at this location are necessary for understanding the comprehensive fracture of the whole bone. The goal of this study is to identify fracture toughness in terms of J integral and fracture mechanism at the interface between cortical and cancellous bone. For this purpose, single edge notch bend (SENB) specimens were prepared from bovine proximal femur according to ASTM-E399 standard. Bone samples were prepared such that half of the sample width consists of cortical bone and other half of the width was cancellous bone; this interfacial bone is referred as a corticellous bone. Elastic-plastic fracture mechanics was used to measure fracture toughness. The J integral (both elastic and plastic) was used to quantify the fracture toughness. The plastic part of J integral value (Jpl) of corticellous specimen was 9310 J m-2, and shown to be 27 times of the J integral of the elastic part (Jel), 341 J m-2. The total J integral of the corticellous bone was found to be 9651 J m-2, which is close to two times of the cortical bone, 4731 J m-2. This study observed that J integral of corticellous bone is higher than the cortical bone since more energy is required for plastic deformation of corticellous bone due to crack branches and slowdown at the interface between cortical and cancellous bone.

A macro-micro FE and ANN framework to assess site-specific bone ingrowth around the porous beaded-coated implant: an example with BOX® tibial implant for total ankle replacement.

The use of mechanoregulatory schemes based on finite element (FE) analysis for the evaluation of bone ingrowth around porous surfaces is a viable approach but requires significant computational time and effort. The aim of this study is to develop a combined macro-micro FE and artificial neural network (ANN) framework for rapid and accurate prediction of the site-specific bone ingrowth around the porous beaded-coated tibial implant for total ankle replacement (TAR). A macroscale FE model of the implanted tibia was developed based on CT data. Subsequently, a microscale FE model of the implant-bone interface was created for performing bone ingrowth simulations using mechanoregulatory algorithms. An ANN was trained for rapid and accurate prediction of bone ingrowth. The results predicted by ANN are well comparable to FE-predicted results. Predicted site-specific bone ingrowth using ANN around the implant ranges from 43.04 to 98.24%, with a mean bone ingrowth of around 74.24%. Results suggested that the central region exhibited the highest bone ingrowth, which is also well corroborated with the recent explanted study on BOX®. The proposed methodology has the potential to simulate bone ingrowth rapidly and effectively at any given site over any implant surface.

A numerical investigation for the development of functionally graded Ti/HA tibial implant for total ankle replacement: Influence of material gradation law and volume fraction index.

Stress shielding is one of the major concerns for total ankle replacement implants nowadays, because it is responsible for implant-induced bone resorption. The bone resorption contributes to the aseptic loosening and failure of ankle implants in later stages. To reduce the stress shielding, improvements can be made in the implant material by decreasing the elastic mismatch between the implant and the tibia bone. This study proposes a new functionally graded material (FGM) based tibial implant for minimizing the problem of stress shielding. Three-dimensional finite element (FE) models of the intact tibia and the implanted tibiae were created to study the influence of material gradation law and volume fraction index on stress shielding and implant-bone micromotion. Different implant materials were considered that is, cobalt-chromium, titanium (Ti), and FGM with Ti at the bottom and hydroxyapatite (HA) at the top. The FE models of FGM implants were generated by using different volume fractions and the rule of mixtures. The rule of mixtures was used to calculate the FGM properties based on the local volume fraction. The volume fraction was defined by using exponential, power, and sigmoid laws. For the power and sigmoid law varying volume fraction indices (0.1, 0.2, 0.5, 1, 2, and 5) were considered. The geometry resembling STAR® ankle system tibial implant was considered for the present study. The results indicate that FGMs lower stress shielding but also marginally increase implant-bone micromotion; however, the values were within the acceptable limit for bone ingrowth. It is observed that the material gradation law and volume fraction index influence the performance of FGM tibial implants. The tibial implant composed of FGM using power law with a volume fraction index of 0.1 was the preferred option because it showed the least stress shielding.

Printable functionally graded tibial implant for TAR: FE study comparing implant materials, FGM properties, and implant designs.

Tibial implants with functionally graded material (FGM) for total ankle replacement (TAR) can provide stiffness similar to the host tibia bone. The FGM implants with low stiffness reduce stress shielding but may increase implant-bone micromotion. A trade-off between stress shielding and implant-bone micromotion is required if FGMs are to substitute traditionally used Ti and CoCr metal implants. The FGM properties such as material gradation law and volume fraction index may influence the performance of FGM implants. Along with the FGM properties, the design of FGM implants may also have a role to play. The objective of this study was to examine FGM tibial implants for TAR, by comparing implant materials, FGM properties, and implant designs. For this purpose, finite element analysis (FEA) was conducted on 3D FE models of the intact and the implanted tibia bone. The tibial implants were composed of CoCr and Ti, besides them, the FGM of Ti and HA was developed. The FGM implants were modelled using exponential, power, and sigmoid laws. Additionally, for power and sigmoid laws, different volume fraction indices were taken. The effect of implant design was observed by using keel type and stem type TAR fixation designs. The results indicated that FGM implants are better than traditional metal implants. The power law is most suitable for developing FGM implants because it reduces stress shielding. For both power law and sigmoid law, low values of the volume fraction index are preferrable. Therefore, FGM implant developed using power law with 0.1 vol fraction index is ideal with the lowest stress shielding and marginally increased implant-bone micromotion. FGM implants are more useful for keel type fixation design than stem type design. To conclude, with FGMs the major complication of stress shielding can be solved and the longevity and durability of TAR implants can be enhanced.

Assessment of bone ingrowth around beaded coated tibial implant for total ankle replacement using mechanoregulatory algorithm.

The long-term performance of porous coated tibial implants for total ankle replacement (TAR) primarily depends on the extent of bone ingrowth at the bone-implant interface. Although attempts were made for primary fixation for immediate post-operative stability, no investigation was conducted on secondary fixation. The aim of this study is to assess bone ingrowth around the porous beaded coated tibial implant for TAR using a mechanoregulatory algorithm. A realistic macroscale finite element (FE) model of the implanted tibia was developed based on computer tomography (CT) data to assess implant-bone micromotions and coupled with microscale FE models of the implant-bone interface to predict bone ingrowth around tibial implant for TAR. The macroscale FE model was subjected to three near physiological loading conditions to evaluate the site-specific implant-bone micromotion, which were then incorporated into the corresponding microscale model to mimic the near physiological loading conditions. Results of the study demonstrated that the implant experienced tangential micromotion ranged from 0 to 71 µm with a mean of 3.871 µm. Tissue differentiation results revealed that bone ingrowth across the implant ranged from 44 to 96 %, with a mean of around 70 %. The average Young's modulus of the inter-bead tissue layer varied from 1444 to 4180 MPa around the different regions of the implant. The analysis postulates that when peak micromotion touches 30 µm around different regions of the implant, it leads to pronounced fibrous tissues on the implant surface. The highest amount of bone ingrowth was observed in the central regions, and poor bone ingrowth was seen in the anterior parts of the implant, which indicate improper osseointegration around this region. This macro-micro mechanical FE framework can be extended to improve the implant design to enhance the bone ingrowth and in future to develop porous lattice-structured implants to predict and enhance osseointegration around the implant.

Influence of obesity on load-transfer mechanism, contact mechanics, and longevity of cemented acetabular cup.

Objective: This investigation aimed to assess the impact of obesity on the load-transfer mechanism, longevity, and contact mechanics of cemented acetabular cups. Methods: Three obesity scenarios were considered: obese case-I (100-110 kg), obese case-II (120-130 kg), and obese case-III (140-150 kg). Utilising six finite element models, the effects of different bodyweights on load transfer, contact mechanics, and cup longevity during normal walking conditions were assessed. Muscle forces and hip joint reaction forces were adjusted and linearly calibrated based on obesity cases. Results: Elevated stresses in cortical and cancellous bones, as well as the cement mantle, were observed in obese cases, suggesting a heightened risk of loosening and failure of the cemented fixation of the acetabular cup. Additionally, increased contact pressure and micromotion between articulating surfaces were noted in obese individuals, with a gradual escalation from obese case-I to obese case-III. Conclusions: These findings highlight the significant negative impact of obesity on the performance of cemented acetabular cups, emphasizing the importance of considering bodyweight variations in the design and assessment of orthopaedic implants for optimal functionality and durability.

A numerical investigation of stress, strain, and bone density changes due to bone remodelling in the talus bone following total ankle arthroplasty.

Total ankle arthroplasty is the gold standard surgical treatment for severe ankle arthritis and fracture. However, revision surgeries due to the in vivo failure of the ankle implant are a serious concern. Extreme bone density loss due to bone remodelling is one of the main reasons for in situ implant loosening, with aseptic loosening of the talar component being one of the primary reasons for total ankle arthroplasty revisions. This study is aimed at determining the performance and potential causes of failure of the talar component. Herein, we investigated the stress, strain, and bone density changes that take place in the talus bone during the first 6 months of bone remodelling due to the total ankle arthroplasty procedure. Computed tomography scans were used to generate the 3D geometry used in the finite element (FE) model of the Intact and implanted ankle. The Scandinavian Total Ankle Replacement (STAR™) CAD files were generated, and virtual placement within bone models was done following surgical guidelines. The dorsiflexion physiological loading condition was investigated. The cortical region of the talus bone was found to demonstrate the highest values of stress (5.02 MPa). Next, the adaptive bone remodelling theory was used to predict bone density changes over the initial 6-month post-surgery. A significant change in bone density was observed in the talus bone due to bone remodelling. The observed quantitative changes in talus bone density over 6-month period underscore potential implications for implant stability and fracture susceptibility. These findings emphasise the importance of considering such biomechanical factors in ankle implant design and clinical management.

Deciphering inhibitory activity of marine algae Ecklonia cava phlorotannins against SARS CoV-2 main protease: A coupled in-silico docking and molecular dynamics simulation study.

The onset of COVID-19 due to the SARS CoV-2 virus has spurred an urgent need for potent therapeutics and vaccines to combat this global pandemic. The main protease (Mpro) of the virus, crucial in its replication, has become a focal point in developing anti-COVID-19 drugs. The cysteine protease Mpro in SARS CoV-2 bears a significant resemblance to the same protease found in SARS CoV-1. Previous research highlighted phlorotannins derived from Ecklonia cava, an edible marine algae, as inhibitors of SARS CoV-1 Mpro activity. However, it remains unclear whether these marine-derived phlorotannins also exert a similar inhibitory effect on SARS CoV-2 Mpro. To unravel this, our study utilized diverse in-silico methodologies. We explored the pharmacological potential of various phlorotannins (phloroglucinol, triphloretol-A, eckol, 2-phloroeckol, 7-phloroeckol, fucodiphloroethol G, dieckol, and phlorofucofuroeckol-A) and assessed their binding efficacies alongside established Mpro inhibitors (N3 and lopinavir) through molecular docking studies. Among these compounds, five phlorotannins (eckol, 2-phloroeckol, 7-phloroeckol, dieckol, and phlorofucofuroeckol-A) exhibited potent binding affinities comparable to or surpassing N3 and lopinavir, interacting especially with the catalytic residues His41 and Cys145 of Mpro. Moreover, molecular dynamics simulations revealed that these five Mpro-phlorotannin complexes displayed enhanced stability and maintained comparable or slightly reduced compactness. They exhibited reduced conformational changes and increased expansion relative to the Mpro-N3 and/or Mpro-lopinavir complex. Our MM-GBSA analysis further supported these findings. Overall, our investigation highlights the potential of these five phlorotannins in inhibiting the proteolytic function of SARS CoV-2 Mpro, offering promise for anti-COVID-19 drug development.

Repurposing of antimycobacterium drugs for COVID-19 treatment by targeting SARS CoV-2 main protease: An in-silico perspective.

The global mortality rate has been significantly impacted by the COVID-19 pandemic, caused by the SARS CoV-2 virus. Although the pursuit for a potent antiviral is still in progress, experimental therapies based on repurposing of existing drugs is being attempted. One important therapeutic target for COVID-19 is the main protease (Mpro) that cleaves the viral polyprotein in its replication process. Recently minocycline, an antimycobacterium drug, has been successfully implemented for the treatment of COVID-19 patients. But it's mode of action is still far from clear. Furthermore, it remains unresolved whether alternative antimycobacterium drugs can effectively regulate SARS CoV-2 by inhibiting the enzymatic activity of Mpro. To comprehend these facets, eight well-established antimycobacterium drugs were put through molecular docking experiments. Four of the antimycobacterium drugs (minocycline, rifampicin, clofazimine and ofloxacin) were selected by comparing their binding affinities towards Mpro. All of the four drugs interacted with both the catalytic residues of Mpro (His41 and Cys145). Additionally, molecular dynamics experiments demonstrated that the Mpro-minocyline complex has enhanced stability, experiences reduced conformational fluctuations and greater compactness than other three Mpro-antimycobacterium and Mpro-N3/lopinavir complexes. This research furnishes evidences for implementation of minocycline against SARS CoV-2. In addition, our findings also indicate other three antimycobacterium/antituberculosis drugs (rifampicin, clofazimine and ofloxacin) could potentially be evaluated for COVID-19 therapy.

A Paper-Based Multiplexed Serological Test to Monitor Immunity against SARS-COV-2 Using Machine Learning.

The rapid spread of SARS-CoV-2 caused the COVID-19 pandemic and accelerated vaccine development to prevent the spread of the virus and control the disease. Given the sustained high infectivity and evolution of SARS-CoV-2, there is an ongoing interest in developing COVID-19 serology tests to monitor population-level immunity. To address this critical need, we designed a paper-based multiplexed vertical flow assay (xVFA) using five structural proteins of SARS-CoV-2, detecting IgG and IgM antibodies to monitor changes in COVID-19 immunity levels. Our platform not only tracked longitudinal immunity levels but also categorized COVID-19 immunity into three groups: protected, unprotected, and infected, based on the levels of IgG and IgM antibodies. We operated two xVFAs in parallel to detect IgG and IgM antibodies using a total of 40 µL of human serum sample in <20 min per test. After the assay, images of the paper-based sensor panel were captured using a mobile phone-based custom-designed optical reader and then processed by a neural network-based serodiagnostic algorithm. The serodiagnostic algorithm was trained with 120 measurements/tests and 30 serum samples from 7 randomly selected individuals and was blindly tested with 31 serum samples from 8 different individuals, collected before vaccination as well as after vaccination or infection, achieving an accuracy of 89.5%. The competitive performance of the xVFA, along with its portability, cost-effectiveness, and rapid operation, makes it a promising computational point-of-care (POC) serology test for monitoring COVID-19 immunity, aiding in timely decisions on the administration of booster vaccines and general public health policies to protect vulnerable populations.

Experimental validation of numerically predicted strain and micromotion in intact and implanted composite hemi-pelvises.

The failure mechanisms of acetabular prostheses may be investigated by understanding the changes in load transfer due to implantation and using the analysis of the implant-bone micromotion. Computational finite element (FE) models allow detailed mechanical analysis of the implant-bone structure, but their validity must be assessed as a first step, before they can be employed in preclinical investigations. In this study, FE models of composite hemi-pelvises, intact and implanted with an acetabular cup, were experimentally validated. Strains and implant-bone micromotions in the hemi-pelvises were compared with those predicted by the equivalent FE models. Regression analysis indicated close agreement between the measured and FE strains, with a high correlation coefficient (0.95-0.98), a low standard error (SE) (36-53 mu epsilon) and a low error in regression slope (7%-11%). Measured micromotions along three orthogonal directions were small, less than 30 microm, whereas the FE-predicted values were found to be less than 85 .m. Although the trends were similar, the deviations are due to artefacts in experimental measurement and additional imperfections in recreating experimental loading and boundary conditions in the FE model. This supports the FE model as a valid predictor of the measured strain in the composite pelvis models, confirming its suitability for further computational investigations on acetabular prostheses.

A combined FE-hybrid MCDM framework for improving the performance of the conical stem tibial design for TAR with the addition of pegs.

BACKGROUND AND OBJECTIVES: The conical stemmed design of the tibial component for total ankle replacement (TAR) (example Mobility design) uses a single intramedullary stem for primary fixation. Tibial component loosening is a common mode of failure for TAR. Primary causes of loosening are lack of bone ingrowth due to excessive micromotion at the implant-bone interface and bone resorption due to stress shielding after implantation. The fixation feature of the conical stemmed design can be modified with the addition of small pegs to avoid loosening. The aim of the study is to select the improved design for conical stemmed TAR using a combined Finite Element (FE) hybrid Multi-Criteria Decision-Making (MCDM) framework. METHODS: The geometry and material properties of the bone for FE modeling were extracted from the CT data. Thirty-two design alternatives with varying pegs in number (one, two, four, eight), location (anterior, posterior, medial, lateral, anterior-posterior, medial-lateral, equally spaced), and height (5 mm, 4 mm, 3 mm, 2 mm) were prepared. All models were analyzed for dorsiflexion, neutral, and plantarflexion loading. The proximal part of the tibia was fixed. The implant-bone interface coefficient of friction was taken as 0.5. The implant-bone micromotion, stress shielding, volume of bone resection, and surgical simplicity were the important criteria considered for evaluating the performance of TAR. The designs were compared using a hybrid MCDM method of WASPAS, TOPSIS, EDAS, and VIKOR. The weight calculations were based on fuzzy AHP and the final ranks on the Degree of Membership method. RESULTS: The addition of pegs decreased the mean implant-bone micromotions and increased stress shielding. There was a marginal decrease in micromotion and a marginal increase in stress shielding when the peg heights were increased. The results of hybrid MCDM indicated that the most preferable alternative designs were two pegs of 4 mm height in the AP direction to the main stem, two pegs of 4 mm height in the ML direction, and one peg of 3 mm height in the A direction. CONCLUSIONS: Outcomes of this study suggest that the addition of pegs can reduce the implant-bone micromotions. Modified three designs would be useful by considering implant-bone micromotions, stress shielding, volume of bone resection, and surgical simplicity.

The role of the depth of resection of the distal tibia on biomechanical performance of the tibial component for TAR: A finite element analysis with three implant designs.

The depth of resection of the tibia bone in total ankle replacement (TAR) may influence implant-bone micromotion and stress shielding. High implant-bone micromotion and stress-shielding lead to aseptic loosening of the tibial component for TAR. The aim was to improve the outcomes of the different designs of TAR (STAR, Mobility, and Salto) with the variation of the depth of resection of the distal tibia bone. Finite element (FE) models of the implanted tibia with the depth of resection varying from 6 mm to 16 mm and of the intact tibia was prepared. The value of micromotion increased as the depth of resection increased. The micromotion increased in the proximal anterior-posterior portion of the pegs for STAR, the posterior part of the stem for Mobility, and the proximal lateral portion of the keel for Salto with the increase in the depth of resection. Whereas, the stresses (von Mises) decreased in some regions and increased in some regions depending upon the implant design. But overall stresses decreased in the tibia bone. Furthermore, the mean stress shielding increased in all the designs as the depth of resection increased. This in silico study indicated that the depth of resection should be given more importance during TAR surgery. The ideal depth of resection should be minimum i.e., 6 mm based on this FE study.

A new mathematical model of compressive stress-strain behaviour of low viscosity and high viscosity bone cement with different strain rates.

A new mathematical model of compressive stress-strain behaviour of low viscosity (LV) and high viscosity (HV) bone cement has been proposed to capture large uniaxial deformation under constant applied strain rate by incorporating three-term power law. The modeling capacity of the proposed model has been validated using uniaxial compressive test under eight different low strain rates ranging from 1.39 × 10-4 s-1 to 3.53 × 10-2 s-1 for low viscosity and high viscosity bone cement. The well agreement between the model and experimental response suggests that the proposed model can successfully predict rate dependent deformation behavior for Poly(methyl methacrylate) (PMMA) bone cement. Additionally, the proposed model was compared with the generalized Maxwell viscoelastic model and found to be in good agreement. The comparison of compressive responses over low strain rates for LV and HV bone cement reveals their rate-dependent compressive yield stress behaviour along with a higher value of compressive yield stress of LV bone cement compared to HV bone cement. For example, at the strain rate of 1.39 × 10-4 s-1 the mean value of compressive yield stress of LV bone cement was found to be 64.46 MPa, whereas for HV bone cement it was 54.00 MPa. Moreover, the modeling of experimental compressive yield stress with the Ree-Eyring molecular theory suggests that the variation of yield stress of PMMA bone cement can be predicted using two processes Ree-Eyring theory. The proposed constitutive model might be useful to characterize large deformation behaviour with high accuracy for PMMA bone cement. Finally, both variants of PMMA bone cement also exhibit ductile-like compressive behaviour below the strain rate of 2.1 × 10-2 s-1, whereas above this threshold strain rate, brittle-like compressive failure behavior is observed.